While the intrinsic nervous system of the alimentary tract regulates almost all aspects of digestive function, the development and function of the enteric nervous system has received relatively little investigative attention. Disorders of the enteric nervous system have been implicated in a variety of human disease processes, usually without clear mechanism. Reflecting this deficiency of basic information, current therapy for enteric neuropathy is empiric and usually ineffective. This proposal continues basic investigations focused on the development and function of the enteric nervous system, based on the belief that these studies are crucial to an improved understanding of the pathogenesis of enteric neuropathy. The research plan seeks to: 1) examine morphological development of myenteric neurons in response to established and novel growth factors; 2) determine basement membrane substrate requirements for expression of developmental signals by enteric neurons; 3) examine systems of signal transduction involved in trophic activities; 4) study regulation of early-response and cytoskeletal genes exerted by neural growth factors; and 5) to examine development of cholinergic neurotransmission as a functional correlate. Using novel in vitro approaches, the proposal integrates physiological studies with important advances in cellular and molecular biology, in an effort to provide new insights into neural control of enteric function.